Drug Interaction:
No drug-drug interactions were observed between pertuzumab and trastuzumab, or between
pertuzumab and docetaxel
Indication:
PERJETAR (pertuzumab) Injection, for intravenous use
Initial U.S. Approval: 2012
WARNING: CARDIOMYOPATHY and EMBRYO-FETAL TOXICITY
See full prescribing information for complete boxed warning.
Cardiomyopathy: PERJETA can result in subclinical and clinical cardiac failure
manifesting as CHF, and decreased LVEF.
Evaluate cardiac function prior to and during treatment.
Discontinue PERJETA treatment for a confirmed clinically significant decrease
in left ventricular function.
Embryo-fetal Toxicity: Exposure to PERJETA can result in embryo-fetal death
and birth defects. Studies in animals have resulted in oligohydramnios,
delayed renal development, and death. Advise patients of these risks an
the need for effective contraception.
RECENT MAJOR CHANGES
Indications and Usage (1.2) 09/2013
Dosage and Administration (2.1) 04/2013 Dosage and Administration (2.1, 2.2) 09/2013
Contraindications (4) 09/2013
Warnings and Precautions (5.2, 5.3, 5.4, 5.5) 09/2013
Drug Name- Perjeta
Active Ingredient - Pertuzumab
To treat patients with HER2 -positive late stage (metastatic ) cancer
Indication-
Treat patients with HER2 -positive late-stage(metastatic) cancer
Approved by FDA on 8-6-2012 (Ref- FDA Approved List- 2012)
Proprietary Name- PERJETA INJECTION*
Established Name- Pertuzumab
Applicant- GENETECH INC.
Indication- For use in combination with Transtuzumab and Docetaxel
for the Neoadjuvant treatment of patients with HER-2 -positive
Locally Advanced Inflammatory, or Early stage Breast Cancer
(either greater than 2cm in diameter or node positive) as a part
of complete regimen for early breast cancer
Approval Date- September 30,2013
Approved by U.S.FDA (Ref- FDA approved List- 2013)
Adverse Reaction:
Metastatic Breast Cancer
The most common adverse reactions (> 30%) with PERJETA in combination
with trastuzumab and docetaxel were diarrhea, alopecia, neutropenia, nausea,
fatigue, rash, and peripheral neuropathy.
Neoadjuvant Treatment of Breast Cancer
The most common adverse reactions (> 30%) with PERJETA in combination
with trastuzumab and docetaxel were alopecia, diarrhea, nausea, and neutropenia.
The most common adverse reactions (>30%) with PERJETA in combination
with trastuzumab and docetaxel when given for 3 cycles following 3 cycles of FEC
were fatigue, alopecia, diarrhea, nausea, vomiting, and neutropenia.
The most common adverse reactions (>30%) with PERJETA in combination
with docetaxel, carboplatin, and trastuzumab (TCH) were fatigue, alopecia,
diarrhea, nausea, vomiting, neutropenia, thrombocytopenia, and anemia.
Contra-Indications:
CONTRAINDICATIONS
PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab
or to any of its excipients.
WARNINGS AND PRECAUTIONS
Embryo-fetal toxicity: Fetal harm can occur when administered to a pregnant woman.
Left Ventricular Dysfunction: Monitor LVEF and withhold dosing as appropriate.
Infusion-Related Reactions: Monitor for signs and symptoms.
If a significant infusion-associated reaction occurs, slow or interrupt the infusion
and administer appropriate medical therapies.
Hypersensitivity Reactions/Anaphylaxis: Monitor for signs and symptoms.
If a severe hypersensitivity reaction/anaphylaxis occurs, discontinue the infusion
immediately and administer appropriate medical therapies.
HER2 testing: Perform using FDA-approved tests by laboratories with demonstrated
proficiency.
Dosages/ Overdosage Etc:
Indication-
Treat patients with HER2 -positive late-stage(metastatic) cancer
INDICATIONS AND USAGE
PERJETA is a HER2/neu receptor antagonist indicated for:
Use in combination with trastuzumab and docetaxel for treatment of patients
with HER2-positive metastatic breast cancer (MBC) who have not received
prior anti-HER2 therapy or chemotherapy for metastatic disease.
Use in combination with trastuzumab and docetaxel as neoadjuvant treatment
of patients with HER2-positive, locally advanced, inflammatory, or early stage
breast cancer (either greater than 2 cm in diameter or node positive) as part of a
complete treatment regimen for early breast cancer.
This indication is based on demonstration of an improvement in pathological
complete response rate.
No data are available demonstrating improvement in event-free survival
or overall survival.
Limitations of Use: The safety of PERJETA as part of a doxorubicin-containing regimen
has not been established.
The safety of PERJETA administered for greater than 6 cycles for early breast
cancer has not been established.
DOSAGE AND ADMINISTRATION
For intravenous infusion only. Do not administer as an intravenous push or bolus.
The initial PERJETA dose is 840 mg administered as a 60-minute intravenous infusion,
followed every 3 weeks thereafter by 420 mg administered as a 30 to 60 minute
intravenous infusion.
MBC: Administer PERJETA, trastuzumab, and docetaxel by intravenous infusion
every 3 weeks.
Neoadjuvant: Administer PERJETA, trastuzumab, and docetaxel by intravenous
infusion preoperatively every 3 weeks for 3 to 6 cycles.
DOSAGE FORMS AND STRENGTHS
420 mg/14 mL single-use via
Patient Information:
PATIENT COUNSELING INFORMATION
Advise pregnant women and females of reproductive potential that PERJETA
exposure can result in fetal harm, including embryo-fetal death or birth
defects
Advise females of reproductive potential to use effective contraception while
receiving PERJETA and for 6 months following the last dose of PERJETA
Advise nursing mothers treated with PERJETA to discontinue nursing or
discontinue PERJETA, taking into account the importance of the drug to
the mother
Encourage women who are exposed to PERJETA during pregnancy to enroll
in the MotHER Pregnancy Registry by contacting 1-800-690-6720
Pharmacology/ Pharmacokinetics:
1. Mechanism of Action
Pertuzumab targets the extracellular dimerization domain (Subdomain II) of the human
epidermal growth factor receptor 2 protein (HER2) and, thereby, blocks ligand-dependent
heterodimerization of HER2 with other HER family members, including EGFR, HER3, and
HER4. As a result, pertuzumab inhibits ligand-initiated intracellular signaling through two
major signal pathways, mitogen-activated protein (MAP) kinase, and phosphoinositide 3-kinase
(PI3K). Inhibition of these signaling pathways can result in cell growth arrest and apoptosis,
respectively. In addition, pertuzumab mediates antibody-dependent cell-mediated cytotoxicity
(ADCC).
2. Pharmacokinetics
Pertuzumab demonstrated linear pharmacokinetics at a dose range of 25 mg/kg. Based on a population PK analysis that included patients, the median clearance (CL) of pertuzumab was 24 L/day and the median half-life was 18 days. With an initial dose of 840 mg followed by a maintenance dose of 420 mg every three weeks thereafter, the steady-state concentration of pertuzumab was reached after the first maintenance dose.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
Risk Summary
There are no adequate and well-controlled studies of PERJETA in pregnant women.
Based on findings in animal studies, PERJETA can cause fetal harm when
administered to a pregnant woman. The effects of PERJETA are likely to be present
during all trimesters of pregnancy.
If PERJETA is administered during pregnancy, or if a patient becomes pregnant while
receiving PERJETA, the patient should be apprised of the potential hazard to the fetus.
2.Nursing Mothers
It is not known whether PERJETA is excreted in human milk, but human IgG is excreted in
human milk. Because many drugs are secreted in human milk and because of the
potential for serious adverse reactions in nursing infants from PERJETA, a decision
should be made whether to discontinue nursing, or discontinue drug, taking into
account the elimination half-life of PERJETA and the importance of the drug to
the mother
3.Pediatric Use
The safety and effectiveness of PERJETA have not been established in pediatric
patients.
4. Geriatric Use
Of patients who received PERJETA in Study 1, 60 patients (15%) were 65 years
of age and 5 patients (1%) were 75 years of age. No overall differences in efficacy
and safety of PERJETA were observed between these patients and younger patients
Manufacturer Details